Abstract

Introduction

Materials & Methods

Results

Discussion & Conclusion

References

Discussion
Board

As neoplastic cells require Fe to sustain their rapid growth, Fe chelators may have potential as anti-cancer agents. While a high Fe binding affinity is essential, other properties such as membrane permeability may influence the site of Fe chelation and the mechanisms by which they exert their antineoplastic actions. In this study a range of Fe chelators were investigated for their ability to inhibit cellular proliferation and Fe uptake from transferrin by hepatoma cells (rat hepatoma cell lines HTC and McArdle 7777 and human hepatoma cell lines HepG2 and HuH7). Chelators assessed included membrane permeable ferric chelators (eg. pyridoxal isonicotinoyl hydrazone (PIH) and 1,2 dimethyl-3-hydroxypyrid-4-one (L1)), membrane impermeable ferric chelators (eg, diethylenetriaminepentaacetic acid (DTPA) and ethylenediaminetetraacetic acid (EDTA)) membrane permeable ferrous chelators (eg, a a dipyridine (DP)) and membrane impermeable ferrous chelators (eg, bathophenanthroline disulphonic acid (BPS)). The effects of the chelators on cell growth were examined using the MTT proliferation assay. The effects of the chelators on Fe and Tf uptake were measured by incubating cells (in exponential phase of growth) in MEM containing 59Fe-Tf-125I and the chelator. Fe uptake into all cell types was markedly reduced by PIH and L1, consistent with their high level of inhibition of cellular proliferation. However for several other chelators (eg, DTPA) the level of inhibition in cellular proliferation and Fe uptake differed markedly. These observations will be discussed in relation to the properties of the chelators and the cell lines.

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Presentation Number SAkicic0473
Keywords: Fe chelator, cancer, hepatoma